Table 1.
Classification of Charcot-Marie-Tooth Disease (CMT)
| Type* | Locus/gene | Prominent phenotype |
|---|---|---|
| CMT1: | ||
| CMT1A | 17p11.2/PMP22 duplication | Prototype of CMT1 |
| CMT1B | 1q21–23/MPZ | May present as an axonal neuropathy |
| CMT1C | 16p12–13/SIMPLE/LITAF | Almost indistinguishable from CMT1A |
| CMT1D | 10q21–22/EGR2 | Severe dysmyelination with cranial nerve involvement |
| CMT1F | 8p21/NEFL | Lacks de/dysmyelination, but CV is in the range of CMT1 |
| CMT with nerve susceptibility to mechanical stress: | ||
| HNPP | 17p11.2/PMP22 deletion | Focal sensory loss and weakness; tomacula |
| Others? | ||
| CMTX: | ||
| CMTX1 | X-chromosome/GJB1 | Intermediate range of CV |
| CMT2: | ||
| CMT2A | 1p36/MFN2 | Early & late onset; optic atrophy/hearing loss |
| CMT2B | 3q21/RAB7 | Prominent sensory loss and foot ulcers |
| CMT2C | 12q23/TRPV4 | Vocal cord paralysis; skeletal deformities |
| CMT2D | 7p15/GARS | Motor deficits in upper limbs |
| CMT2E | 8p21/NEFL | Lacks de/dysmyelination, but CV is in the range of CMT1 |
| CMT2F | 7q/HSP27 | Classical CMT2 or distal SMA |
| CMT2G | 12q12–13/unknown | |
| CMT2L | 12q24/HSP27 | Classical CMT2 or distal SMA |
| CMT4: | ||
| CMT4A | 8q13/GDAP1 | Demyelination or axonal; vocal cord paralysis |
| CMT4B1 | 11q22/MTMR2 | Myelin folding |
| CMT4B2 | 11p15/MTMR13 | Myelin folding |
| CMT4C | 5q32/SH3TC2(KIAA1985) | |
| CMT4D | 8q24/NDRG1 | Severe; hearing loss; CNS involvement |
| CMT4E | 10q21/EGR2 | Severe dysmyelination or amyelination |
| CMT4F | 19q13/PRX | Myelin folding—tomacula |
| CMT4H | 12q11/FGD4 | |
| CMT4J | 6q21/FIG4 | Rapidly progressive asymmetric weakness |
| ARCMT2A | 1q21/LMNA | Proximal muscle weakness; muscular dystrophy; cardiomyopathy |
| DI-CMT: | ||
| DI-CMTA | 10q24 | |
| DI-CMTB | 19q12/DNM2 | |
| DI-CMTC | 1p34/YARS | |
| Inherited brachial plexopathy | ||
| HNPP | 17p11.2/PMP22 deletion | No pain/unilateral arm weakness |
| HNA | 17q25/SEPT9 | Severe pain/arm weakness & atrophy |
CNS, Central nervous system; SMA, spinal muscular dystrophy; CV
Note:
*
Dejerine-Sottas Disease (DSD) has been defined clinically with onset by 2 years of age, delayed motor milestones, and severe motor/sensory and skeletal deficits. DSD is caused by autosomal dominant mutations in PMP22, MPZ, and EGR2, thus should not be viewed as a subtype of CMT due to the heterogeneity of genetic causes and inconsistent pathology ranging from severe dysmyelination to predominant axonal loss. Due to its unique phenotypic features, we recommend listing hereditary neuropathy with liability to pressure palsies (HNPP) as a separate group.